2021_Preparation and Characterization of Cationic Β-Cyclodextrin-Insulin Loaded Alginate Nanoparticles For Oral Delivery

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date 2021-12-08
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id 15370
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originalfilename 15370_deac4d4bfc5af86.pdf
person Hazem Choukaife
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spelling 15370 https://intelek.unisza.edu.my/intelek/pages/view.php?ref=15370 https://intelek.unisza.edu.my/intelek/pages/search.php?search=!collection3 General Document Malaysia Library Staff (Top Management) Library Staff (Management) Library Staff (Support) Terengganu Faculty of Pharmacy English application/pdf 1.5 Server storage Scanned document Universiti Sultan Zainal Abidin UniSZA Private Access Universiti Sultan Zainal Abidin SAMBox 2.3.4; modified using iTextSharp™ 5.5.10 ©2000-2016 iText Group NV (AGPL-version) 139 2021-12-08 15370_deac4d4bfc5af86.pdf 2021_Preparation and Characterization of Cationic Β-Cyclodextrin-Insulin Loaded Alginate Nanoparticles For Oral Delivery Alginate Nanoparticles Hazem Choukaife Drug delivery systems Copyright©PWB2025 Diabetes mellitus is a chronic metabolic condition, which is characterised by high blood glucose level due to defect in insulin producing cells. The current diabetes therapy is subcutaneous insulin injections. However, frequent daily injections may lead to low patient compliance and substantial inconvenience. Several alternative routes of insulin delivery are being investigated including oral, pulmonary, nasal, buccal and inhaled routes. Although the oral route is the most convenient way of drug delivery, insulin is vulnerable to rapid degradation in the stomach and low intestinal permeation. The polymeric nanocarriers have recently attracted considerable attention as oral delivery vehicles for insulin. These nanocarriers may protect insulin from degradation and facilitate insulin absorption through transcellular and/or paracellular route. This project aimed to fabricate cationic β-cyclodextrin (CβCD)-insulin-loaded alginate nanoparticles and evaluate their potential as oral insulin delivery system. CβCD were prepared from β-cyclodextrin (β-CD) through a one-step polycondensation by utilizing choline chloride (CC) to provide ammonium group and epichlorohydrin (EP) to form polymeric chains. The synthesised CβCD was confirmed through nuclear magnetic resonance (NMR) spectroscopy. Afterwards, insulin was complexed with CβCD via both inclusion and electrostatic attraction with the aim of enhancing the insulin release profile. This complex was investigated using Fourier transform infrared (FT-IR) and then encapsulated into calcium alginate nanoparticles by two-step procedure based on ionic gelation method. The size, polydispersity index (PDI), zeta potential, encapsulation efficiency (EE), surface morphology and cumulative drug release of the nanoparticles were estimated using different characterization techniques such as; Dynamic light scattering (DLS), transmission electron microscopy (TEM) and ultraviolet-visible (UV-Vis) spectrophotometry. In vitro cytotoxicity activity of the nanoparticles against HT-29 cells were evaluated by 3-(4,5-dimethylthiazol-2-yl)-2,5 diphenyl-2H-tetrazolium bromide (MTT) assay using different nanoparticles concentrations. CβCD-insulin-loaded alginate nanoparticles were characterized by reduced particle size as well as improved encapsulation efficiency and minimal insulin release into simulated gastric fluid (SGF) as a result of the strong electrostatic attraction between insulin and CβCD. The optimised nanoparticle formulation exhibited particle size at 339.53 ± 20.88 nm, encapsulation efficiency at 81.88 ± 1.72 % and cumulative insulin release in (SGF) at 9.36 ± 0.49 % compared with 445.4 ± 152.94 nm, 45.65 ± 1.49 % and 49.69 ± 1.75 % of that without CβCD, respectively. MTT assay revealed that all formulations were considered non-toxic toward HT-29 cells. The present study advocated that CβCD-insulin-loaded alginate nanoparticles can be a promising system for enhancing insulin oral delivery. Dissertations, Academic Sila masukkan subject wajib Dissertations, Academic. Terima kasih... Insulin-Loaded Nanoparticles Oral Drug Delivery Thesis
spellingShingle 2021_Preparation and Characterization of Cationic Β-Cyclodextrin-Insulin Loaded Alginate Nanoparticles For Oral Delivery
state Terengganu
subject Drug delivery systems
Dissertations, Academic
summary Diabetes mellitus is a chronic metabolic condition, which is characterised by high blood glucose level due to defect in insulin producing cells. The current diabetes therapy is subcutaneous insulin injections. However, frequent daily injections may lead to low patient compliance and substantial inconvenience. Several alternative routes of insulin delivery are being investigated including oral, pulmonary, nasal, buccal and inhaled routes. Although the oral route is the most convenient way of drug delivery, insulin is vulnerable to rapid degradation in the stomach and low intestinal permeation. The polymeric nanocarriers have recently attracted considerable attention as oral delivery vehicles for insulin. These nanocarriers may protect insulin from degradation and facilitate insulin absorption through transcellular and/or paracellular route. This project aimed to fabricate cationic β-cyclodextrin (CβCD)-insulin-loaded alginate nanoparticles and evaluate their potential as oral insulin delivery system. CβCD were prepared from β-cyclodextrin (β-CD) through a one-step polycondensation by utilizing choline chloride (CC) to provide ammonium group and epichlorohydrin (EP) to form polymeric chains. The synthesised CβCD was confirmed through nuclear magnetic resonance (NMR) spectroscopy. Afterwards, insulin was complexed with CβCD via both inclusion and electrostatic attraction with the aim of enhancing the insulin release profile. This complex was investigated using Fourier transform infrared (FT-IR) and then encapsulated into calcium alginate nanoparticles by two-step procedure based on ionic gelation method. The size, polydispersity index (PDI), zeta potential, encapsulation efficiency (EE), surface morphology and cumulative drug release of the nanoparticles were estimated using different characterization techniques such as; Dynamic light scattering (DLS), transmission electron microscopy (TEM) and ultraviolet-visible (UV-Vis) spectrophotometry. In vitro cytotoxicity activity of the nanoparticles against HT-29 cells were evaluated by 3-(4,5-dimethylthiazol-2-yl)-2,5 diphenyl-2H-tetrazolium bromide (MTT) assay using different nanoparticles concentrations. CβCD-insulin-loaded alginate nanoparticles were characterized by reduced particle size as well as improved encapsulation efficiency and minimal insulin release into simulated gastric fluid (SGF) as a result of the strong electrostatic attraction between insulin and CβCD. The optimised nanoparticle formulation exhibited particle size at 339.53 ± 20.88 nm, encapsulation efficiency at 81.88 ± 1.72 % and cumulative insulin release in (SGF) at 9.36 ± 0.49 % compared with 445.4 ± 152.94 nm, 45.65 ± 1.49 % and 49.69 ± 1.75 % of that without CβCD, respectively. MTT assay revealed that all formulations were considered non-toxic toward HT-29 cells. The present study advocated that CβCD-insulin-loaded alginate nanoparticles can be a promising system for enhancing insulin oral delivery.
title 2021_Preparation and Characterization of Cationic Β-Cyclodextrin-Insulin Loaded Alginate Nanoparticles For Oral Delivery
title_full 2021_Preparation and Characterization of Cationic Β-Cyclodextrin-Insulin Loaded Alginate Nanoparticles For Oral Delivery
title_fullStr 2021_Preparation and Characterization of Cationic Β-Cyclodextrin-Insulin Loaded Alginate Nanoparticles For Oral Delivery
title_full_unstemmed 2021_Preparation and Characterization of Cationic Β-Cyclodextrin-Insulin Loaded Alginate Nanoparticles For Oral Delivery
title_short 2021_Preparation and Characterization of Cationic Β-Cyclodextrin-Insulin Loaded Alginate Nanoparticles For Oral Delivery
title_sort 2021_preparation and characterization of cationic β-cyclodextrin-insulin loaded alginate nanoparticles for oral delivery